Abstract
Novel enantiomers and diastereoisomers structurally related to σ ligand (+)-MR200 were synthesized to improve σ(1)/σ(2) subtype selectivity. The selective σ(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of κ opioid analgesia. The σ(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods*
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Cyclopropanes / agonists*
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Cyclopropanes / antagonists & inhibitors*
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Cyclopropanes / chemical synthesis*
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Drug Design
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Humans
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Kinetics
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Magnetic Resonance Spectroscopy / methods
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Models, Chemical
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Muscle Contraction / drug effects
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Piperidines / agonists*
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Piperidines / antagonists & inhibitors*
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Piperidines / chemical synthesis*
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Protein Binding
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Receptors, Opioid, delta / drug effects*
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Time Factors
Substances
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(+)-methyl 2-((4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)methyl)-1-phenylcyclopropanecarboxylate
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Cyclopropanes
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Piperidines
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Receptors, Opioid, delta